The eye is a common site of granulomatosis with polyangiitis. A collaborative study.

BACKGROUND: Ocular manifestations of granulomatosis with polyangiitis (GPA) have been reported in a limited number of studies and with largely variable frequency. Here we report on the clinical, diagnostic, and therapeutic features of a cohort of 63 GPA patients, with particular regard to 22 of them with ophthalmic involvement (35%). METHODS: Clinical manifestations, results of immunological findings, histopathological pictures, imaging data, Birmingham Vasculitis Activity Score, therapeutic regimens, and outcomes were retrospectively analyzed. At diagnosis, in addition to a structured clinical assessment, all patients underwent a comprehensive ophthalmologic examination. RESULTS: The most frequently involved organs were kidneys, lungs, ear/nose/throat, and eyes. Ocular manifestations were bilateral in 32%. The three most commonly diagnosed ophthalmologic manifestations were scleritis (36%), retro-orbital pseudotumor or orbital mass (23%), and episcleritis (13%). Ocular and systemic involvement were simultaneously present at onset in 41% of the patients; systemic involvement was followed by ocular lesions in 36%; ocular inflammation was followed by systemic manifestations in 18%; and an orbital mass in the absence of systemic disease characterized 5%. Glucocorticoids plus cyclophosphamide and glucocorticoids plus rituximab were the combined therapies most frequently employed during remission induction and remission maintenance, respectively. Persistent ophthalmologic and extra-ocular remissions were achieved in 77 and 64% of the patients, respectively. One to three systemic relapses were diagnosed in 7 patients (31.8%). At the last follow-up, a visual outcome 20/40 or better in 31 (70%) of 44 eyes was determined. CONCLUSIONS: The eye was involved in over one third of our patients with GPA. Increased awareness, early diagnosis, and multi-specialty collaboration are critical in achieving a favorable outcome of GPA.

A rare case of lacrimal sac dirofilariasis confirmed by polymerase chain reaction.

A 69-year-old female presented with complaints of persistent watering in the left eye for the past 8 years. She underwent a left external dacryocystorhinostomy (DCR) 8 years ago. On examination, left lacrimal passage irrigation showed regurgitation of fluid from opposite punctum. She underwent a revision external DCR with bicanalicular intubation and a portion of fibrosed sac was sent for histopathological examination (HPE). HPE showed a Microfilarial worm with surrounding granulomatous inflammation. Polymerase chain reaction (PCR) on the DNA extracted from the specimen identified the species to be Dirofilaria repens. Dirofilariasis is an accidental zoonotic infection in humans. Due to its migration, the worm can affect ocular and periocular structures. There are two case reports of perilacrimal dirofilariasis. This is the first case to report a filarial worm in the lacrimal sac causing chronic inflammation which probably led to failure of DCR. Treatment of choice is the complete eradication of the worm. PCR aids in the identification of species.

Diagnostic efficacy of elevated serum angiotensin-converting enzyme and lymphopenia between presumed sarcoid uveitis and presumed tubercular uveitis.

PURPOSE: To evaluate the diagnostic efficacy of elevated serum angiotensin-converting enzyme (sACE) and lymphopenia in presumed sarcoid and tubercular uveitis. METHODS: A single-centre retrospective study was conducted on a cohort of 755 adult patients with uveitis between January 2019 and June 2020. Demographic, clinical and laboratory data were retrieved from our hospital database. Measurements of serum angiotensin-converting enzyme (sACE) and lymphocyte counts were analysed. RESULTS: The mean age of the patients was 41 ± 13 years. Presumed sarcoid uveitis was diagnosed in 50 (7%) patients, presumed tubercular uveitis in 222 (29.4%) and other uveitic entities noted in 483 (64%). Intermediate and posterior uveitis were the most common anatomical diagnosis in presumed sarcoid uveitis (59% and 20%, respectively) and in presumed tubercular uveitis (46% and 38%, respectively). Elevated sACE was noted in 76% of presumed sarcoid uveitis and 46% in presumed tubercular uveitis. The combination of high serum angiotensin-converting enzyme along with lymphopenia was only in 17% in presumed sarcoid uveitis and 9.7% in presumed tubercular uveitis. sACE was found to be a significant risk factor for presumed sarcoid uveitis with an odds ratio of 3.603 (p < 0.002), and in presumed tubercular uveitis odds ratio was not significant with odds ratio of 1.19. Lymphopenia was not found to be a significant factor in both groups. CONCLUSION: Elevated sACE activity was an independent risk factor for presumed sarcoid uveitis over lymphopenia alone or in combination with lymphopenia.

Retino-choroidal evaluation of the macular region in eyes with tubercular serpiginous-like choroiditis using swept-source optical coherence tomography angiography.

AIM: To analyse the alterations in retino-choroidal angioarchitecture in eyes with active tubercular serpiginous-like choroiditis (TB-SLC) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This prospective cross-sectional study enrolled 34 eyes diagnosed with TB-SLC and 34 age-matched healthy controls. Data acquisition with SS-OCTA using the PLEX Elite 9000 (Carl Zeiss Meditec Inc., Dublin, CA, USA) with a 6 × 6 mm pattern centered on the foveal center was done. Automated retinal vessel length density (VLD) and perfusion density (PD) and foveal avascular zone architecture were obtained from the ARI hub. Choroidal vascularity index (CVI) and choriocapillaris flow deficits (CCFD) were obtained using Image J. RESULTS: Eyes with TB-SLC showed significantly reduced vessel indices in all retinal layers (P < 0.05), decreased CVI (P = 0.001) and increased CCFD (P = 0.001) as compared to healthy eyes. CCFD was increased significantly in the involved quadrants in eyes with TB-SLC when compared with the uninvolved quadrants and corresponding healthy quadrants in control subjects. CCFD showed a significant negative correlation with visual acuity (r = - 0.46, P = 0.006). CONCLUSION: Eyes with TB-SLC manifest reduced VLD and PD, decreased CVI and increased CCFD. The CCFD alterations are non-uniform in these eyes, mainly located under the regions with disease activity.

Choroidal neovascularization in 111 eyes of children and adolescents.

PURPOSE: To describe the clinical features, management, and outcomes of choroidal neovascularization (CNV) in children less than 18 years of age. METHODS: This was a retrospective, case control study of 111 eyes of 96 patients. CNV was clinically diagnosed in all patients. Eyes were classified as those that were observed (Controls; Group 1) or those that had treatment (Cases; Group 2). CNV was categorized as regressed, persistent, or recurrent in order to evaluate the anatomical outcomes. RESULTS: Of 96 patients, 68(71%) were male. Mean presenting age was 11.4 ± 3.4 years (median = 11 years, range = 1-17 years). CNV was bilateral in 15(16%) patients. Of 111 eyes, 38 eyes had treatment (Cases) and 73 eyes did not (Natural history group or Controls). Subfoveal CNV was seen in majority of cases (59%). Most common etiology was post-inflammatory (38%), followed by trauma (16%). Eyes were classified as those that were observed (controls; Group 1) or those that had treatment (cases; Group 2). In group 1, spontaneous regression of CNV was seen in 26(36%) eyes and there was no recurrence in this group. In group 2 following treatment, 25(66%) of 38 eyes achieved complete regression at mean 4.9 months and was persistent in 5 eyes. CNV recurrence was seen in 10 eyes with the mean time to first recurrence being 9 months. At presentation, mean best-corrected visual acuity (BCVA) of eyes with subfoveal CNV was logMAR 0.99 that improved to logMAR 0.63 with treatment. Mean follow-up was 17 months. CONCLUSION: CNV results in significant visual decline in children; most commonly of post-inflammatory etiology. Treatment achieves high regression rates, albeit with limited visual improvement.

Further evidence of the association of latent Mycobacterium tuberculosis in Eales' disease.

PURPOSE: To find out association of Eales' disease with Mycobacterium tuberculosis. METHODS: A retrospective study was done recruiting patients visiting the uvea clinic with diagnosis of Eales' disease from 2015-2019. Seventy-nine eyes of 50 patients diagnosed as Eales' disease underwent Mantoux test, QuantiFERON-TB Gold test, high resolution computed tomography (HRCT) of the chest and anterior chamber or vitreous tap for TB genome polymerase chain reaction(PCR). RESULTS: The study included 41 males and 9 females. The mean age of the patient was 35.62 ± 11.49 y. Out of 50 patients, 42% (n = 21) patients had unilateral involvement. Mantoux test was positive in 73% patients. QuantiFERON-TB Gold test was positive in 56% patients. HRCT chest was suggestive of pulmonary tuberculosis in 34% patients. Out of 6 patients, PCR from anterior chamber tap showed TB genome positive in 2 (33.3%) patients. Out of 9 patients, vitreous tap PCR was positive for TB genome in 2 (22.2%) patients. CONCLUSIONS: Our study showed that one or more tests were positive for TB in Eales' disease suggesting a pivotal role of TB as a primary etiology for this disease. We conclude that Eales' disease is associated with Mycobacterium tuberculosis infection.

Ocular manifestations of HLA B 27 associated uveitis: a study of 255 cases from a tertiary eye care centre from South India.

PURPOSE: To describe the clinical profile of HLA B-27-associated uveitis in Indian population. METHOD: We conducted a retrospective review of medical records of 431 eyes of 255 consecutive patients with HLA B-27-associated uveitis, presented to our institute between 2012 and 2017. RESULT: The study observed a male preponderance (75.7%) and the mean age of patients was 35.6 ± 13.3 years. A total of 412 (95.3%) eyes had anterior uveitis, 17(3.9%) eyes had anterior and intermediate uveitis and 3 eyes (0.7%) had intermediate uveitis. Retinal vasculitis was detected in four eyes (0.9%). A total of 176 patients (69%) in the study had evidence of systemic disease and 85% patients developed recurrences. In addition to the treatment with topical and oral steroid, immunosuppressive was required in 39.6% patients and 4% patients received biological therapy. The majority of the eyes (78.4%) had a good visual outcome, while 61 (14.2%) eyes had moderate visual impairment and 32 (7.4%) eyes had severe visual impairment at the time of final follow-up. CONCLUSION: HLA-B27-associated uveitis can be associated with higher number of posterior segment involvement than it is estimated and aggressive therapy in moderate-to-severe uveitis can prevent severe visual impairment in these patients.

Intravitreal rituximab monotherapy for management of eyes with vitreoretinal lymphoma: initial experience from India.

PURPOSE: To evaluate treatment outcomes and complications of intravitreal rituximab (IVR) monotherapy for eyes with vitreoretinal lymphoma (VRL). METHODS: Patients diagnosed with 'isolated primary VRL' or 'VRL with remission of systemic disease' and treated with IVR (1 mg/0.1 ml) between June 2014 and June 2019 were included in this retrospective, interventional case series. Injections were repeated at monthly intervals until complete resolution. All patients signed a written informed consent form. Institutional review board approval was obtained. RESULTS: Twelve eyes of 7 patients with VRL were treated with 77 IVR injections at mean 6.42 injections per eye (median = 5; range = 2-13) for complete resolution at mean 8.16 ± 4.62 months (median = 6.97 months; range = 1.97-14.33 months). Mean age at presentation was 53.3 years (median = 54 years; range = 34-74 years). Patients were co-managed with medical oncologist and periodically evaluated. Complications included anterior uveitis (n = 6), raised intraocular pressure (n = 3), posterior synechiae (n = 2), vitreous haemorrhage (n = 1), pre-retinal haemorrhage (n = 1), retinal detachment (n = 1), posterior subcapsular cataract (n = 2) and sectoral iris atrophy (n = 1). Recurrences were seen in 3 eyes (25%), which eventually achieved complete resolution with treatment. None of the patients had systemic involvement or death during follow-up. Mean follow-up was 18.73 ± 8.83 months (median = 21.60 months; range = 7.37-32.67 months). CONCLUSION: Intravitreal rituximab monotherapy is effective in management of vitreoretinal lymphoma in patients with isolated ocular disease.

Ocular sarcoidosis: clinical experience and recent pathogenetic and therapeutic advancements.

PURPOSE: To describe the ocular manifestations in a cohort of patients with systemic sarcoidosis (SS). Recent advances in the pathophysiology, diagnosis, and therapy of SS are also discussed. METHODS: Data from 115 Italian patients diagnosed between 2005 and 2016 were retrospectively reviewed. All but the first 17 patients underwent a comprehensive ophthalmologic examination. The diagnosis was based on clinical features, the demonstration of non-caseating granulomas in biopsies from involved organs, and multiple imaging techniques. Data on broncho-alveolar lavage fluid analysis, calcemia, calciuria, serum angiotensin-converting enzyme levels and soluble interleukin-2 receptor levels were retrieved when available. RESULTS: Ocular involvement, detected in 33 patients (28.7%), was bilateral in 29 (87.9%) and the presenting feature in 13 (39.4%). Anterior uveitis was diagnosed in 12 patients (36.4%), Löfgren syndrome and uveoparotid fever in one patient each (3%), intermediate uveitis in 3 patients (9.1%), posterior uveitis in 7 (21.2%), and panuveitis in 9 (27.3%). First-line therapy consisted of corticosteroids, administered as eyedrops (10 patients), sub-Tenon's injections (1 patient), intravitreal implants (9 patients), or systemically (23 patients). Second-line therapy consisted of steroid-sparing immunosuppressants, including methotrexate (10 patients) and azathioprine (10 patients). Based on pathogenetic indications that tumor necrosis factor (TNF)-α is a central mediator of granuloma formation, adalimumab, targeting TNF-α, was employed in 6 patients as a third-line agent for severe/refractory chronic sarcoidosis. CONCLUSION: Uveitis of protean type, onset, duration, and course remains the most frequent ocular manifestation of SS. Diagnostic and therapeutic advancements have remarkably improved the overall visual prognosis. An ophthalmologist should be a constant component in the multidisciplinary approach to the treatment of this often challenging but intriguing disease.

Elemental concentrations in Choroid-RPE and retina of human eyes with age-related macular degeneration.

Heavy metals, metallic and toxic elements are reported to play an essential role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). This study was aimed to measure the concentrations of these elements in choroid-RPE and retina of human donor eyes with and without age-related macular degeneration associated changes. Human cadaver donor eyeballs were obtained from the CU Shah eye bank, Sankara Nethralaya Eye Hospital, India, after removal of the cornea. 39 control and 51 AMD donor eyes were used in this study. Alabama grading was done on the histopathological sections to identify early and late age-related macular degeneration changes. Concentrations of lead, cadmium, chromium, cobalt, nickel, arsenic and selenium were determined in choroid-RPE and retina using Inductively Coupled Plasma Mass Spectrometer (ICP-MS). Further, gene expression of oxidative stress-related genes, Nrf-2, HO-1, GCLC, GCLM, and detoxification related gene GSTpi was performed. The data were analyzed for statistical significance using Graph Pad® Prism 5 software. Donor eyes with early and late AMD had significantly higher levels of lead, cadmium, chromium, arsenic, and nickel in choroid-RPE and retina compared to the control eyes. Selenium was significantly increased in late AMD compared to control. No significant difference was observed in the levels of cobalt between eyes with and without AMD. Decreased transcript levels of oxidative stress-related genes were observed in the choroid-RPE and retinal tissues. Nrf-2 (p < 0.05), HO-1 and GCLC expressions were lowered in the retina of AMD, whereas GCLM and GSTpi expressions were decreased (p < 0.05) with an increase in HO-1 in choroid-RPE of AMD. This study provides evidence that alterations of the heavy metals and toxic elements along with oxidative stress may play a role in the pathogenesis of AMD.

Periocular thelaziasis presenting as an orbital mass - a case report.

Thelazia callipaeda is a rare parasitic infestation caused by spiruroid nematode of the genus Thelazia. We report a case of a 74-year-old gentleman who presented with a painless swelling of left lower lid since 15 days. Examination revealed a firm mobile mass along the inferior orbital rim. Magnetic Resonance Imaging showed a well-defined preseptal cystic lesion and Ultrasound screening revealed multiple mobile worms within. Patient underwent cyst excision in toto under local anesthesia. Four long refractile worms were isolated from within the cyst cavity. Species identification confirmed the parasite as Thelazia callipaeda. Periocular thelaziasis usually presents as free floating worms in the conjunctival sac, anterior chamber or vitreous cavity. It is important to be aware of this rare entity which should be considered as a differential diagnosis in endemic areas.

Postsurgical sympathetic ophthalmia: retrospective analysis of a rare entity.

PURPOSE: To describe clinical manifestations, management and visual outcome in postsurgical sympathetic ophthalmia (SO). METHODS: Retrospective study. RESULTS: Mean age of the patients was 41.1 years, and males were affected 1.8 times than the female. Vitrectomy and scleral buckling were the most common inciting surgeries followed by cataract surgery. Among 10 eyes with anterior uveitis, mutton-fat keratic precipitate was seen in only two eyes. Mean follow-up duration was 1556.50 ± 1470.75 days. Vision significantly improved in 11 patients (78.6%; p = 0.005). CONCLUSION: Postsurgical SO is a rare entity, but it is a bilateral blinding disease and SO following surgical intervention can have variable presentations. Rapid, effective management of postsurgical sympathetic ophthalmia can give improved visual outcomes.

Cholesterol granuloma: a case series & review of literature.

BACKGROUND: Cholesterol granuloma (CG) is a foreign body reaction to crystallized cholesterol. Orbitofrontal CG is a rare entity with few cases reported in literature. It is usually seen in young to middle-aged males with a history of trauma. Computed tomography features include hypodense lesion-causing bone erosion. CG has typical histopathological features with cholesterol clefts, multinucleated giant cells, histiocytes, foamy macrophages, and altered blood pigments. Management is by total excision of the lesion with curettage of the underlying bone to prevent recurrence. MATERIAL & METHOD: We present an interventional case series of five patients of orbitofrontal CG, two of them females. RESULT: None of the patients gave a history of trauma. Management was by excision of the lesion and curettage confirmed with a 30° rigid endoscope. CONCLUSION: Cholesterol granulomas can present as superior orbital mass lesions in the absence of trauma.

Detection of Mycobacterium tuberculosis with nested polymerase chain reaction analysis in enucleated eye ball in Eales' disease.

Nested polymerase chain reaction (nPCR) was performed on enucleated eyeball for detection of Mycobacterium tuberculosis (M. tb) genome in a patient with Eales' disease. PCR analysis in all previous studies has been done mainly using aqueous, vitreous and epiretinal membranes from these patients. Paraffin wax embedded tissue section of the enucleated eyeball was analyzed by histopathology and nPCR targeting MPB64 gene and IS6110 region of M. tb genome. Lymphocytic infiltration was seen in the vitreous, iris and the retinal tissue. Ziehl Neelsen stain was negative for acid fast bacilli. Caseation necrosis was not seen in any section. Agarose gel electrophoretogram showed positive results with 200 bp specific amplified product targeting MPB64 gene, whereas nPCR targeting IS6110 region was negative. Since biopsy proven M. tb is extremely difficult in ocular tissues due to extensive necrosis, the nPCR technique aided in the diagnosis.

A Giant Apocrine Hidrocystoma Presenting as Lacrimal Gland Mass.

Apocrine hidrocystomas are cysts resulting from obstruction of the apocrine sweat gland ducts. They are usually solitary and seen in the head and neck areas. Apocrine hidrocystomas are rarely seen in the orbit with very few adult cases published in literature until now.

Interobserver agreement in clinical grading of vitreous haze using alternative grading scales.

PURPOSE: To evaluate the reliability of clinical grading of vitreous haze using a new 9-step ordinal scale versus the existing 6-step ordinal scale. DESIGN: Evaluation of diagnostic test (interobserver agreement study). PARTICIPANTS: A total of 119 consecutive patients (204 uveitic eyes) presenting for uveitis subspecialty care on the study day at 1 of 3 large uveitis centers. METHODS: Five pairs of uveitis specialists clinically graded vitreous haze in the same eyes, one after the other using the same equipment, using the 6- and 9-step scales. MAIN OUTCOME MEASURES: Agreement in vitreous haze grade between each pair of specialists was evaluated by the κ statistic (exact agreement and agreement within 1 or 2 grades). RESULTS: The scales correlated well (Spearman's ρ = 0.84). Exact agreement was modest using both the 6-step and 9-step scales: average κ = 0.46 (range, 0.28-0.81) and κ = 0.40 (range, 0.15-0.63), respectively. Within 1-grade agreement was slightly more favorable for the scale with fewer steps, but values were excellent for both scales: κ = 0.75 (range, 0.66-0.96) and κ = 0.62 (range, 0.38-0.87), respectively. Within 2-grade agreement for the 9-step scale also was excellent (κ = 0.85; range, 0.79-0.92). Two-fold more cases were potentially clinical trial eligible on the basis of the 9-step than the 6-step scale (P<0.001). CONCLUSIONS: Both scales are sufficiently reproducible using clinical grading for clinical and research use with the appropriate threshold (≥ 2- and ≥ 3-step differences for the 6- and 9-step scales, respectively). The results suggest that more eyes are likely to meet eligibility criteria for trials using the 9-step scale. The 9-step scale appears to have higher reproducibility with Reading Center grading than clinical grading, suggesting that Reading Center grading may be preferable for clinical trials.

Evolution of research in diagnosis and management of uveitis over four decades in India.

Uveitis and its complications are more common in the developing world, in which the condition occurs in up to 714 per 100,000 in the population and accounts for up to 25% of all blindness. In India, the ophthalmic sub speciality of uveitis greatly evolved in the last four decades. In the early decades most of the studies were epidemiological studies. In recent years, more research has been published due to tremendous advancements in clinical diagnosis, laboratory investigations and ancillary test and treatment modalities. In this review article, we did a medline search with key words 'uveitis' and 'India', and selectively incorporated articles showing the evolution of this sub-speciality in India.

Efficacy of adalimumab in noninfectious pediatric uveitis: Analysis of 29 eyes from a tertiary eye care center in India.

PURPOSE: To describe the treatment outcomes of adalimumab in noninfectious pediatric uveitis. METHODS: The electronic medical records of children with noninfectious uveitis were reviewed retrospectively. The visual improvement and ocular inflammation were assessed according to the Standardization of Uveitis Nomenclature criteria before and after treatment with adalimumab. RESULTS: Twenty-nine eyes of 16 patients were included. The mean age of children was 9.4 ± 3.8 years. There were eight (50%) males and eight (50%) females. Juvenile idiopathic arthritis was the most common cause of uveitis in these children (N = 10, 62.5%), followed by Behçet's disease (N = 3, 18.75%) and Vogt-Koyanagi-Harada disease (N = 2, 12.5%). One child (6.25%) was diagnosed with Crohn's disease. Nine (56.3%) children were previously treated with methotrexate, one each with mycophenolate mofetil (MMF) (6.3%), azathioprine (6.3%), and tofacitinib (6.3%), and one child received MMF followed by azathioprine and cyclosporine before shifting to adalimumab. Three (18.8%) children did not receive prior immunosuppressive therapy. The average number of adalimumab injections given was 20.3 ± 12.0 at an interval of 2 weeks. The mean follow-up duration was 22.2 ± 16.6 months. Disease inactivity was achieved in 28 (96.6%) eyes at last visit ( P < 0.001). The best-corrected visual acuity (BCVA) improved from 0.48 ± 0.6 logMAR (logarithm of minimum of resolution) units at baseline to 0.20 ± 0.2 logMAR units at last visit ( P = 0.018). Disease remission was achieved in 23 (79.3%) eyes at the third month ( P = 0.001). CONCLUSION: Adalimumab is effective in the treatment of pediatric noninfectious uveitis by achieving disease inactivity, reducing the recurrence rate and improving BCVA. The drug is safe and well tolerated.

Masquerade syndrome: A review of uveitic imposters.

Masquerade syndromes in uveitis are complex clinical conditions where non-inflammatory diseases mimic uveitic manifestations, often leading to diagnostic and therapeutic challenges. This review delves into the diverse spectrum of masquerade syndromes, categorizing them into neoplastic and non-neoplastic entities. We explore the prevalence of primary intraocular lymphoma, leukaemia, retinoblastoma, and other malignancies, as well as conditions like retinitis pigmentosa and endophthalmitis that can present as uveitis. Through detailed analysis of symptoms, diagnostic methods, and treatment approaches, the review emphasizes the importance of considering masquerade syndromes in differential diagnoses to prevent mismanagement. The synthesis of current knowledge aims to enhance clinicians' ability to discern these complex presentations, advocating for a multidisciplinary approach to diagnosis and care, thereby improving patient outcomes in cases of uveitic masquerade syndromes.